Tuesday, October 23, 2018

√ On The Threshold Of Cell Therapy For Parkinson’S Disease

By Jeanne Loring


Dopamine neurons derived from a Parkinson √ On the threshold of cell therapy for Parkinson’s disease
Dopamine neurons derived from a Parkinson’s disease patient’s iPSCs (Tyrosine hydroxylase). Image source: Loring lab.

There are ten million people in the world who have Parkinson’s disease. 125,000 of these are living in California.  People with the disease often have to step away from their jobs because the main symptoms – tremor or freezing up of muscles – make it difficult to get through a whole day of work.


Parkinson’s disease is caused by the loss of a specific neuron type in the brain.  The dopamine neurons in the region of the brain called the substantia nigra die over time, and by the time the disease is diagnosed, at least half are gone.  There is no drug therapy that can bring them back.


Because a single cell type in a specific area of the body is lost, it has long been argued that Parkinson’s disease is the ideal sasaran for a cell replacement therapy using dopamine neurons derived from embryonic or induced pluripotent stem cells.


That is exactly the strategy quickly moving forward right now by four research groups worldwide, who have joined forces to share their information in an initiative called “GForce-PD”.


GForce was started in 2014 by three research groups:  Jun Takahashi (Japan) a partnership between Roger Barker (UK) and Malin Parmar (Sweden), and Lorenz Studer (New York).


A new report describes the results of the GForce meeting in May of this year in Kyoto: “Human Trials of Stem Cell-Derived Dopamine Neurons for Parkinson’s Disease: Dawn of a New Era”. Our kegiatan (called “Summit”) is included along with the other three in the report.


My team was delighted to be invited to join G-Force this year at the Kyoto meeting to contribute our own neuron replacement therapy kegiatan to the initiative. While the other groups are using allogeneic (unmatched) cells and will give the patients immunosuppressive drugs, we plan to use patient-specific (autologous) iPSCs to make neurons for each patient, which will keep the cells from being rejected.  Our project was started in 2011 with funding from hundreds of people who donated to the Summit for Stem Cell Foundation and a grant from the National Stem Cell Foundation, and we recently were awarded a grant from the California Institute for Regenerative Medicine (CIRM).


The Kyoto meeting was unprecedented in my experience.  Instead of competing, the four groups cooperated and shared plans for their proposed clinical trials.  We agreed to harmonize our trials and stay in communication about our progress.  All of us plan to start clinical trials within two years.


Support for GForce projects


Each of the GForce members has to obtain independent support from his or her own funding agencies.


NYSTEM, New York’s stem cell agency, has invested about $23 million, nearly 7% of its total budget to date ($354 million) in Lorenz Studer’s kegiatan to use hESCs to produce dopamine neurons from human embryonic stem cells (hESCs) for transplantation (allogeneic therapy).  This year Studer and a Toronto investigator founded a company, BlueRock Therapeutics, with a remarkable investment of $225 million that will pay for the planned clinical trials.


The UK/Sweden project has been supported with more than $27 million from the European Union (EU)(http://cordis.europa.eu/project/rcn/94248_en.html; http://cordis.europa.eu/project/rcn/110638_en.html), in addition to funds from other agencies.  They are also using hESCs (allogeneic therapy).


Specific funding for the Japanese project is not reported, but it is part of CiRA, the stem cell institute headed by Dr. Shinya Yamanaka, that receives hundreds of millions from the Japanese government. Again, this project is using allogeneic therapy, with iPSCs from a single individual.


Unfortunately, CIRM has not provided nearly as much support for Parkinson’s disease therapy as the other agencies.  Although CIRM has invested in California scientists for basic research to study PD over the last 10 years, it wasn’t until a year ago that they finally funded a grant for development of a stem cell-based PD therapy.  Our CIRM grant to develop an autologous therapy is for $2.3 million, a tenth as much as the other GForce projects and less than one percent of CIRM’s total $3 billion budget.


Since my team has been recognized by the international GForce initiative devoted to safe effective therapy for PD, we hope that CIRM will follow the example of New York, the EU, and Japan, and invest more in our project to provide neuron replacement therapy for Californians with Parkinson’s disease.


While we hope to gain more support from CIRM, we are determined to follow through with our clinical trial, with or without CIRM.  It will just be more difficult without their help. The patients and their advocates inspire us, and we won’t let them down.



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